tbuckley/cabot-search huggingface dataset:
OTHR-19. Disordered cell migration in the cerebral cortex caused by Lin28A overexpression and Wnt pathway activation in neural precursor cells
Authors: Jelena Navolic, Maximilian Middelkamp, Piotr Sumislawski, Lisa Ruck, Christoph Krisp, Matthias Dottermusch, Hartmut Schlüter, Julia E Neumann
Journal: Neuro-Oncology (2022)

Abstract LIN28A overexpression and mutations of the Wnt pathway gene CTNNB1 have been described in rare malignant brain tumors of early childhood. In order to investigate the interplay of the oncogenic proteins Lin28A and Ctnnb1 during embryonal brain development, we overexpressed these components in neural progenitor cells in vivo. The sole overexpression of either Lin28A, stabilized Ctnnb1 (Ctnnb1Δex3) or the combination of both in hGFAP-positive forebrain precursor cells did not lead to brain tumor formation but resulted in distinct phenotypes in the cerebral cortex during embryonal development. The hGFAP-cre::IsI-Lin28A (GL) mouse model showed transiently increased proliferation in the cerebral ventricular zone and proper isocortical layering. hGFAP-cre::Ctnnb1Δex3fl/+ (GB) and hGFAP-cre::Ctnnb1Δex3fl/+::IsI-Lin28A (GBL) mice developed a hydrocephalus and showed disturbed cortical layering. GB mice displayed cerebral hypoplasia with a thinned cortex, while the GBL cortices showed variable thickness. Immunostainings with the pial marker Laminin and dendritic marker Map2c revealed a porous pia mater and aggregations of neurons above the pial border in the GBL model at embryonal day 14 (E14.5). At later embryonal stage (E18.5), the GBL model showed also large blood vessels located in deeper cortical layers. Proteome analyses of GB and GBL cortices revealed decreased abundance of the Lissencephaly associated component Reelin-receptor Lrp8 compared to hGFAP-cre control mice. Additionally, we found 92 proteins, which were altered specifically in the GBL mouse model. These results indicate that the co-expression of Lin28A and Ctnnb1Δex3 in neural precursor cells does not lead to brain tumor formation but results in neuronal migration disturbances with ectopic neurons in the subarachnoid area. Whereas the GB phenotype is reminiscent of human lissencephaly type I, GBL brain morphology showed similarities to neuronal overmigration observed in the migration disorder of human Cobblestone (Type II) Lissencephaly.
Insights into the advanced non-small cell lung cancer patient journey: Treatment decision-making, preferences, and quality of life considerations.
Authors: Paul Wheatley-Price, Andrea Stern Ferris, Luciana Holtz De Camargo Barros, Adriana Mancera Font, Carly Ornstein, Daniel Saez, Ewelina Szmytke, Stefania Vallone, Suepattra Grace May, Gerasimos Konidaris, Hampton Shaddock
Journal: Journal of Clinical Oncology (2022)

e21129 Background: Individuals with advanced non-small-cell lung cancer (aNSCLC) who have undergone multiple lines of prior therapy face a poor prognosis and limited treatment options, significantly impacting quality of life (QoL). This exercise explored European, North, and South American patient advocate perspectives on QoL and its relation to treatment decision-making and preferences in aNSCLC. Methods: A global aNSCLC patient advocacy advisory board was convened with organizations from Europe, US, Canada, and Brazil, asking participants about QoL and treatment side effects, and how these relate to subsequent care and treatment decision-making. The discussion was moderated by an oncologist, transcribed, and analyzed using thematic analysis. Results: Preserving one’s independence was highlighted as a key component of QoL, with advocates noting that tumor-related symptoms and treatment toxicities have a substantial negative impact on an individual’s ability to engage in daily activities. Fatigue – both physical and psychological – is especially burdensome, particularly for those who have undergone multiple lines of therapy. Participants also noted the need for more accessible care (e.g., telehealth appointments, oral therapies) that fits into the routines of individuals and caregivers. The importance of palliative care and its ability to improve QoL was noted, showing the need for health systems to better integrate palliative care into treatment regimens. Finally, participants noted that treatment priorities change as individuals undergo subsequent lines of therapy, with participants noting the importance of independence and QoL in later stages of therapy, and thus must be assessed regularly by the care team. Conclusions: Individuals with aNSCLC place importance on consideration of QoL when making treatment decisions, particularly those related to maintaining independence. While there remains a need for additional and more effective therapies, an integrated and accessible care approach, with patient-provider communication focusing on maintaining QoL and independence, should be a priority.
Intraoperative touchless gesture interaction with 3D virtual models during laparoscopic partial nephrectomy: Pilot experience with ICON3D technology
Authors: D. Amparore, F. Piramide, E. Checcucci, P. Verri, A. Pecoraro, S. De Cillis, A. Piana, G. Volpi, M. Sica, S. Piscitello, M. Burgio, P. Alessio, G. Busacca, M. Della Corte, A. Bellin, G. Cattaneo, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2022)
REGOMUNE: Phase II study of regorafenib plus avelumab in solid tumors—Results of the gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) cohort.
Authors: Sophie Cousin, Carine A. Bellera, Jean Philippe Guégan, Fabienne Portales, Antoine Hollebecque, Jean Philippe Metges, Philippe Alexandre Cassier, Carlos A. Gomez-Roca, Fanny Bouteiller, Michèle Kind, Jean Palussière, Simon Pernot, Isabelle Soubeyran, Alban Bessede, Antoine Italiano
Journal: Journal of Clinical Oncology (2022)

4125 Background: There is no standard treatment for patients (pts) with advanced extra-pulmonary neuroendocrine tumors (NET) and carcinomas (NEC) after failure of chemotherapy in the metastatic setting. PD-1/PD-L1 expression is frequent in these tumors. Combining anti-PD1/PDL1 agents with anti-angiogenics has been shown to be synergistic in several tumor models. Methods: This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of regorafenib (R) (160 mg QD 3weeks/4) + Avelumab (A) (10 mg/kg every 2 weeks) combination in pts with advanced or metastatic grade 2 or 3 (G2/3) gastroenteropancreatic (GEP)-NET or GEP-NEC. The primary endpoint was the confirmed objective response rate, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between May 2019 and Apr. 2021, 46 pts were enrolled in 6 centers. Median age was 63 (range 31 – 80). 10 pts presented with a NEC and 36 pts with a G2/3 NET. Median follow-up was 6.5 months (95% CI: 5.3 - 9.6). Median number of previous treatment lines was: 2 (range 0 – 8). 39 (84.8%) pts experienced at least 1 dose modification or treatment interruption. The most common grade 3/4 adverse events were : Hypertension (13% of pts), fatigue (13%), and diarrhea (11%). One death was related to the treatment. Among the 42 assessable pts, 7 (16.7%) achieved a partial response: 6 pts with a G2/3 NET and 1 patient with a NEC. 22 (52.4%) pts demonstrated stable disease, 22 (52.4%) pts had tumor shrinkage and 10 (23.8%) pts had progressive disease. 3 (7.1%) pts were inevaluable as per RECIST. The median duration of response was 15.5 months (95%CI: 3.7 - not reached (NR)). The median PFS and OS were 5.5 months (95% CI: 3.6 – 9.2) and NR respectively. One year OS rate was 69.4 % (95% CI: 45.1 % – 84.5 %). Conclusions: REGOMUNE is the largest prospective study ever conducted in pts with grade 2/3 GEP-NET or GEP-NEC refractory to cytotoxic chemotherapy. The R+A combination has significant clinical activity in pts with refractory disease. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.
OTHR-05. Visual impairment in children with a newly diagnosed brain tumor: a Dutch prospective nationwide cohort study
Authors: Myrthe Nuijts, Inge Stegeman, Tom Seeters, Carlien Bennebroek, Nicole Naus, Giorgio Porro, Michelle van Egmond-Ebbeling, Saskia Imhof, Antoinette Schouten- van Meeteren
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: Visual impairment is a serious adverse effect in children with a brain tumor. To date, visual impairment is often underestimated and unrecognized, while early detection of visual impairment is important to potentially preserve the visual function. Our aim was to assess the prevalence and type of abnormal ophthalmological findings in an unselected cohort of children with a newly diagnosed brain tumor and to identify potential oncological and clinical risk factors. PATIENTS AND METHODS: In this prospective nationwide cohort study, we included children, aged 0-18 years, with a newly diagnosed brain tumor in the Netherlands between May 2019 and August 2021. A comprehensive ophthalmological examination (including orthoptic evaluation, visual acuity, visual fields and funduscopy) was performed at diagnosis. Multivariable logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of the risk factors. RESULTS: In total, 170 children were included (43.5% female; median age [interquartile range], 8.3 [3.9 – 13.0] years; 48.2% infratentorial tumors, 31.2% midline tumors and 20.6% cerebral hemispheres tumors). Overall, 101 children (59.4%) presented with visual symptoms at diagnosis. The most common findings on ophthalmological examination were papilledema (52.4%), gaze deficits (33.5%), visual field defects (28.1%), nystagmus (24.8%), strabismus (19.9%) and decreased visual acuity (8.6%). The risk of papilledema was associated with older age in years (OR 1.2, 95% CI 1.1 – 1.3) and hydrocephalus (OR 14.8, 95% CI 5.4 – 40.0). Visual field defects were detected more frequently in children with a tumor located in the cerebral hemisphere (OR 4.5, 95% CI 1.3 – 15.3) or midline (OR 7.0, 95% CI 2.2 – 21.9). CONCLUSIONS: More than 50% of the children had abnormal ophthalmological findings at brain tumor diagnosis. These findings emphasize the necessity of standardized ophthalmological surveillance and the importance of awareness of health care providers of ophthalmological abnormalities in this patient group.
Identifying tumor cells at the single-cell level using machine learning
Authors: Jan Dohmen, Artem Baranovskii, Jonathan Ronen, Bora Uyar, Vedran Franke, Altuna Akalin
Journal: Genome biology (2022)

Abstract Tumors are complex tissues of cancerous cells surrounded by a heterogeneous cellular microenvironment with which they interact. Single-cell sequencing enables molecular characterization of single cells within the tumor. However, cell annotation—the assignment of cell type or cell state to each sequenced cell—is a challenge, especially identifying tumor cells within single-cell or spatial sequencing experiments. Here, we propose ikarus, a machine learning pipeline aimed at distinguishing tumor cells from normal cells at the single-cell level. We test ikarus on multiple single-cell datasets, showing that it achieves high sensitivity and specificity in multiple experimental contexts.
Radiation therapy and associated cardiovascular outcomes in patients with Hodgkin’s lymphoma.
Authors: Shivani Dalal, Krunalkumar Patel, Atif Mahmoud Hussein, Boula Gattas, Akash Patel, Misha Dalal, Thanh Nguyen, Umang Patel
Journal: Journal of Clinical Oncology (2022)

e19528 Background: Hodgkin’s lymphoma (HL) is a lymphoid neoplasm, with lymphadenopathy with constitutional symptoms as presenting manifestations. The treatment is guided by the clinical stage of disease, and is curable in about 75% of the patients. Advances in cancer therapeutics have improved survival rates, however treatment-related toxicities have become a competing cause of late mortality. Radiation therapy (RT) and chemotherapy have historically been the pillars of curative treatments for HL. RT to the thorax is associated with substantial risk for the development of cardiovascular (CV) disease including pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multi-centre studies with a sufficient duration of CV follow-up. Through this study we aim to determine the CV co-morbidities and outcomes of patients with HL treated with and without RT. Methods: We identified hospitalized adult patients with HL and divided them into patients with and without history of radiation therapy from October 2015 to December 2018 from the National Inpatient Sample Database using ICD 10 codes. We further determined demographics, baseline characteristics, associated CV co-morbidities, mortality, length of stay and hospitalization costs among patients with HL with and without history of RT. SAS 9.4 software was used for statistical analysis. Results: We captured 86,325 patients hospitalized with HL during the study period out of which 11,030 patients had history of RT. The patient cohort with RT was noted to have higher prevalence of hypertension (40.7 vs 37.1%), heart failure with reduced ejection fraction (9.2 vs 6.4%), heart failure with preserved ejection fraction (9.2 vs 5.9%), coronary artery disease (33.6 vs 20.3%), atrial fibrillation (19.2 vs 14%), aortic valve disease (10.1 vs 3.8%), mitral valve disease(5.6 vs 2.7%), pulmonary hypertension (9.6 vs 4.6%), and pleural effusion(9.7 vs 6.8%) as compared to patients without history of RT. The study did not show any statistically significant difference in length of stay or in-hospital mortality in the two groups. Conclusions: This study revealed significantly higher prevalence of multiple CV co-morbidities among HL survivors treated with RT. CV disease is now the most common non malignancy related cause of death in radiation-treated cancer survivors. Awareness and early identification of cardiac complications is crucial survivors. There are currently no consensus guidelines to dictate the optimal surveillance of recipients of thoracic radiation. Therefore through this study we aim to shine light on the importance of early surveillance and collaboration between oncologists and cardiologists in the management of the cancer survivors with history of RT.
Immunotherapy in Hispanic patients with advanced non-small cell lung cancer: A real-world data.
Authors: Mauricio Lujan, Mauricio Lema, Beatriz Preciado, Camila Lema, Jorge Egurrola, Andres Felipe Cardona Zorrilla, Diego Mauricio Gonzalez, William Armando Mantilla, Luis Pino, Gustavo Rojas, Diego Andres Gomez-Abreo, Isabel Munevar, Raimundo Manneh, Ray Manneh Kopp, Jose F. Lobaton, Esteban Calle, Mariana Borras, Ivan Camilo Triana, Mateo Pineda, Diego Moran Ortio
Journal: Journal of Clinical Oncology (2022)

e21094 Background: Nivolumab is a human programmed death receptor-1 (PD-1) blocking antibody, used as treatment option in patients with advanced non-small cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second- or third-line therapy in patients with advanced NSCLC. Methods: This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as second (2L) or third-line (3L) treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective reponse rate to treatment (ORR). OS and PFS were estimated with the Kaplan-Meier method. Statistical analysis was carried out using SPSS version 21.0. Results: Eleven centers distributed across the country (Colombia) participated. Data from 178 patients were included. The median follow-up was 26.8 months (IQR 20.3 - 40.4). Women represented 51.7% of the population, and the median age was 63 years (IQR 56-72 years). Nivolumab was commonly used as a 2L treatment. The ORR with nivolumab as 2L treatment was 21.0%. The median PFS and OS were 5.5 months (95%CI: 4.5 – 6.5) and 12.4 months (95%CI: 10.8 – 14.0), respectively. In 3L the ORR with nivolumab was 15.0%. The overall incidence of adverse events was 1.7%. Conclusions: Nivolumab effectiveness and safety in this scenario was consistent with than reported by previous trials and other real world data.
Role of PSA density in prediction of significant prostate cancer among Asian men with MRI-guided biopsies: A multicenter evaluation
Authors: A. Mok, J.J. Leow, C. Chiang, P.F. Hsieh, W. Lam, W.C. Tsang, H.C. Chan, M.C. Law, C. Leung, C.M. Li, H.S. So, P.L. Liu, W.H. Au, Y.H. Fan, T.P. Lin, J.Y. Teoh, J.H. Tsu, C.F. Ng, H.C. Wu, T.W. Tan, E. Chiong, C.Y. Huang, P.K-F. Chiu
Journal: European Urology (2022)
Evaluation of tumor responses and overall survival in patients with recurrent glioblastoma (GBM) from a phase IIa trial of a CMV vaccine immunotherapeutic candidate (VBI-1901).
Authors: Patrick Y. Wen, David A. Reardon, Deborah Anne Forst, Eudocia Quant Lee, Brittany Haas, Teresa Daoud, Tamara Berthoud, Francisco Diaz-Mitoma, David E Anderson, Andrew B. Lassman, Fabio Massaiti Iwamoto
Journal: Journal of Clinical Oncology (2022)

2014 Background: Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4 + and CD8 + T cells are most frequently directed against the gB and pp65 antigens, respectively, which are immunogenic targets in a CMV-based GBM immunotherapeutic. Methods: A total of 20 first-recurrent GBM patients were enrolled, with Karnofsky Performance Status of at least 70, across 2 arms of the Phase IIa extension phase to receive VBI-1901 (a gB/pp65 enveloped virus-like particle [eVLP]) adjuvanted with either GM-CSF (given intradermally) or AS01 B (given intramuscularly) (NCT03382977). Patients were vaccinated with VBI-1901 every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Results: 10 patients (6 women, 4 men) with a median age of 58 (33-67 yrs) were enrolled into the GM-CSF arm and 10 patients (3 women, 7 men) with a median age of 65 (40-67) enrolled into the AS01 B arm. The 12-month OS rates for the GM-CSF and AS01 B arms were 60% and 70%, respectively; the 18-month OS rate for the GM-CSF arm was 30%, and for the AS01 B arm is expected to be 30%-40% (data has not yet matured). Two durable partial responses (locally determined by RANO) have been observed in the GM-CSF arm, with one patient progression-free and on protocol after 2 years with a tumor size reduction of 93% relative to start of treatment. Immunological analyses demonstrate that prolonged, monthly dosing with VBI-1901 does not lead to immunological tolerance. Dynamic boosting and loss in the peripheral blood of CMV-specific CD4 Tem cells after treatment with VBI-1901 formulated with GM-CSF may correlate with tumor responses. Conclusions: The U.S. FDA granted Fast Track Designation to VBI-1901 adjuvanted with GM-CSF in first-recurrent GBM patients, and an expansion of the ongoing trial with this formulation in this patient population, with the addition of randomization with a contemporaneous control arm, is anticipated to begin in H1 2022. Acknowledgement: GlaxoSmithKline Biologicals SA provided the AS01 B adjuvant used in this study. Clinical trial information: NCT03382977.
LGG-32. Integrated biologic, radiologic and clinical analysis of pediatric low-grade gliomas during and after targeted therapy treatment
Authors: Jessica W Tsai, Jungwhan John Choi, Hakim Ouaalam, Efrain Aguilar Murrillo, Kee Kiat Yeo, Jayne Vogelzang, Cecilia Sousa, Jared K Woods, Keith L Ligon, Simon K Warfield, Pratiti Bandopadhayay, Tabitha M Cooney
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pediatric low grade gliomas (pLGGs) are the most common central nervous system tumor in children, characterized by driver alterations in the RAS and MAPK pathways. Genomic advances have facilitated use of molecular targeted therapies, however their long-term impact on tumor behavior remains critically unanswered. METHODS: We performed an IRB-approved, retrospective chart and imaging review of pLGGs treated with off-label targeted therapy at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center from 2010 to 2020. Volumetric analysis was performed for BRAFV600E and BRAF fusion/duplication driven pLGG subsets. RESULTS: Fifty-five patients were identified (dabrafenib n = 15, everolimus n = 26, trametinib n = 11, and vemurafenib n = 3). Targeted agent was used as first or second-line therapy for 58% (32/55). Median duration of targeted therapy was 0.79 years (0.01 – 4.87), and overall median follow-up was 2.50 years (0.01 – 7.39). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation were 62.1%, 38.2%, and 31.8%, respectively. Mean volumetric change for BRAFV600E mutated pLGG on BRAF inhibitors was -54.11%, and median time to best volumetric response was 8.28 months (n = 12). Median time to largest volume post-treatment was 2.86 months. Mean volumetric change for BRAF fusion/duplication pLGG on MEK inhibitors was +7.34% with median time to best volumetric response of 6.71 months (n = 7). Median time to largest volume post-treatment was 2.38 months. CONCLUSIONS: Our integrated clinical and volumetric data suggest the majority of patients receiving BRAF inhibitors or trametinib achieve reduction in tumor volume while on therapy and that tumor stability can be achieved following targeted therapy cessation. Moreover, volumetric analysis shows promise as a tool to assess targeted therapeutic response in pLGGs.
Robotic radical prostatectomy for prostate cancer in renal transplant recipients: Results from a multicenter series
Authors: G. Marra, M. Agnello, A. Giordano, F. Peretti, F. Soria, M. Oderda, C. Dariane, M.O. Timsit, J. Branchereau, O. Hedli, B. Mesnard, D. Tilki, J. Olsburgh, M. Kulkarni, V. Kasivisvanathan, C. Lebacle, A. Breda, L. Biancone, P. Gontero
Journal: European Urology (2022)
Outbreak of Salmonella Newport linked to imported frozen cooked crayfish in dill brine, Sweden, July to November 2019
Authors: Marie Jansson Mörk, Nadja Karamehmedovic, Anette Hansen, Joanna Nederby Öhd, Mats Lindblad, Emma Östlund, Moa Rehn, Cecilia Jernberg
Journal: Eurosurveillance (2022)

In autumn 2019, the Public Health Agency of Sweden identified a cluster of Salmonella Newport cases by whole genome sequencing (WGS). Cases’ distribution in place and time indicated a nation-wide ongoing outbreak. An investigation was initiated to identify the source and prevent further cases. We conducted a case–case study based on notified salmonellosis cases and a Salmonella trawling questionnaire, comparing 20 outbreak cases and 139 control cases. Food exposures were compared by adjusted odds ratios (aOR) with 95% confidence interval (CI) using logistic regression. Implicated foods were sampled. Outbreak cases were more likely to have consumed crayfish (aOR = 26; 95% CI: 6.3–105). One specific brand of imported frozen, pre-cooked whole crayfish in dill brine was identified as the source. Salmonella Newport was later detected in different batches from retail and in one sample from border control. Isolates from food samples clustered with the human outbreak strain by WGS. Although the retailer made a complete recall, two more cases were identified long afterwards. This investigation demonstrated the successful use of a case–case study and targeted microbiological testing to identify the source. The immediate action taken by the retailer was important to confirm the source and stop the outbreak.